Funds are requested for purchase of an integrated HPLC-Electrospray ionization mass spectrometer with a quadrupole mass filter, a collision chamber and a time of flight analyzer. The instrument will be located in the facilities of the Mass Spectrometry Consortium for the Life Sciences (MSCLS) located in 2100 square feet of newly remodeled space in rooms 43 and 76 of Gortner Laboratories of Biochemistry on the University of Minnesota campus. This facility has provided mass spectrometry services to the life sciences for over 27 years with more than 52,000 samples completed. This instrument will be highly focused on analysis of protein and nucleic acid samples by NIH-funded researchers at the University. Any other time will be distributed among other investigators on this large campus by policies of the internal supervisory committee. The user group includes 15 investigators from many areas of health science research. Examples of proposed research include: "Photosynthetic intermediates and ion channels," "Structure- Function Studies of Fatty Acid Binding Proteins," "Protein Complexes with Telomeres," "Molecular biology of mosquitoes," "Cytoskeleton- based transport within the cell," "Study of FK506 Binding Protein 12 (FKBP12) in muscle," "Vitamin K-dependent proteins. Porins of pathogenic E. coli," "Protein Phosphorylation of erbB2 in response to IL6," "Regulation of Eucaryotic gene expression by estrogen," "Molecular breeding of biosynthetic pathways," "Homeotic genes of the fruit fly encode in development," "Muscle contraction and calcium pump action," and "Sequencing of carcinogen-modified DNA." The primary user group is estimated to require 80% of instrument time. The instrument that is requested was designed for high sensitivity and high resolution in identification of peptides in complex biological mixtures or after elution from gel electrophoretograms. High resolution applies to both the MS and MS/MS modes, making the quadrupole time of flight mass spectrometer critical for many complex experiments such as de novo peptide sequencing and identification of unknown proteins. An accessory nanospray HPLC system for application of small samples is also requested. The instrumentation that is requested is also critical for the emerging area of non-covalent macromolecular complexes.